New mechanism of self-lipid endocytosis mediated by the receptor Mincle

Kostarnoy, A.V.; Gancheva, P.G.; Kireev, I.I.; Solovyev, A.I.; Lepenies, B.; Kulibin, A.Y.; Malolina, E.A.; Scheglovitova, O.N.; Kondratev, A.V.; Sokolova, M.V.; Vorobyeva, D.; Filippova, N.; Kapkaeva, M.R.; Lagarkova, M.A.; Metalnikov, P.S.; Riabenko, E.; Grumov, D.A.; Bobrov, M.A.; Vasilieva, E.; Naroditsky, B.S.; Gintsburg, A.L.

Авторы: Kostarnoy Alexey V., Gancheva Petya G., Kireev Igor I., Solovyev Andrey I., Lepenies Bernd, Kulibin Andrey Yu, Malolina Ekaterina A., Scheglovitova Olga N., Kondratev Alexey V., Sokolova Maria V., Vorobyeva Daria, Filippova Nadezhda, Kapkaeva Marina R., Lagarkova Maria A., Metalnikov Pavel S., Riabenko Evgeniy, Grumov Daniil A., Bobrov Maxim A., Vasilieva Elena, Naroditsky Boris S., Gintsburg Alexander L.
Журнал: Proceedings of the National Academy of Sciences of the United States of America
Том: 119
Номер: 30
Год издания: 2022
Издательство: National Academy of Sciences
Местоположение издательства: United States
Номер статьи: e2120489119
DOI: 10.1073/pnas.2120489119
Аннотация: Cellular lipid uptake (through endocytosis) is a basic physiological process. Dysregulation of this process underlies the pathogenesis of diseases such as atherosclerosis, obesity, diabetes, and cancer. However, to date, only some mechanisms of lipid endocytosis have been discovered. Here, we show a previously unknown mechanism of lipid cargo uptake into cells mediated by the receptor Mincle. We found that the receptor Mincle, previously shown to be a pattern recognition receptor of the innate immune system, tightly binds a range of self-lipids. Moreover, we revealed the minimal molecular motif in lipids that is sufficient for Mincle recognition. Superresolution microscopy showed that Mincle forms vesicles in cytoplasm and colocalizes with added fluorescent lipids in endothelial cells but does not colocalize with either clathrin or caveolin-1, and the added lipids were predominantly incorporated in vesicles that expressed Mincle. Using a model of ganglioside GM3 uptake in brain vessel endothelial cells, we show that the knockout of Mincle led to a dramatic decrease in lipid endocytosis. Taken together, our results have revealed a fundamental lipid endocytosis pathway, which we call Mincle-mediated endocytosis (MiME), and indicate a prospective target for the treatment of disorders of lipid metabolism, which are rapidly increasing in prevalence.
Добавил в систему: Киреев Игорь Игоревич

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New mechanism of self-lipid endocytosis mediated by the receptor Mincleстатья